Fig. 7.

Improvement of glucose metabolism in the KKAy mouse by SeP-neutralizing Ab. a, b Time-dependent change of body weight, blood glucose (a) and plasma mSeP level (b) concentration in KKAy mice (n = 3, means ± s.e.m.). Closed circle, KK; open circle, KKAy. Graphs display the results of densitometric quantification, normalized to major protein (albumin, indicated by black arrowhead) stained with CBB (b, n = 3, means ± s.e.m.). **P < 0.01, *P < 0.05, Tukey-ANOVA (a, b). c, d Improvement of glucose tolerance in KKAy mice administered mSeP-neutralizing Ab. Mouse SeP neutralizing mFHR pAb or control rabbit IgG (25 mg/kg intraperitoneally) was administered 24 h before a glucose tolerance test following the scheme shown in Supplementary Fig. 8a. Glucose (0.3 g/kg body weight) was administered intraperitoneally, and blood glucose was determined at the indicated times (c, n = 5, means ± s.e.m.). *P < 0.05, **P < 0.01, Tukey-ANOVA. Area under the curve for blood glucose levels is shown in d (n = 5, means ± s.e.m.). *P < 0.05, Student's t-test. e–g Improvement of insulin resistance in KKAy mice injected with mSeP-neutralizing Ab. Mouse SeP neutralizing mFHR pAb was administered 48 h before an insulin-tolerance test following the scheme shown in Supplementary Fig. 8a. Insulin (10 U/kg) was administered intraperitoneally, and then blood glucose was determined at the indicated times (e, n = 5, means ± s.e.m.). *P < 0.05, Tukey-ANOVA. Area under the curve for blood glucose levels is shown (f, n = 5, means ± s.e.m.). **P < 0.01, Student's t-test. Phosphorylation of IR and Akt in skeletal muscle of mFHR pAb- or control IgG-treated KKAy mice was evaluated 15 min after insulin administration (g, n = 5, means ± s.e.m.). *P < 0.05, Student's t-test. h Improvement of insulin secretion in KKAy mice treated with mSeP-neutralizing Ab. Blood insulin levels were determined during the glucose-tolerance tests (n = 5, means ± s.e.m.). *P < 0.05, Tukey-ANOVA. Closed circle, control IgG; open circle, mFHR pAb (c, e, h)